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The series was not set in a specific era, but clues throughout the scripts indicated that it took place between the mid-1970s and mid-1980s, with the first moon landing somewhere around 1975. Props were occasionally futuristic (such as a forerunner of today's real-life LCD TVs) but the show's earthly clothing and environs, including automobiles, telephones and other machines, were decidedly 1950s. However, a line of dialogue in "Christmas on the Moon," suggests that the events of that episode take place 2,000 years after the birth of Christ.

Men Into Space was somewhat unusual for a TV action series in that it had numerous recurring characters, but only one --- the protagonist, Col. Edward McCauley (William Lundigan) --- who was in all of the 38 episodes of this series. Tyler McVey appeared in seven episodes as Major General Norgath. Ron Foster appeared five times as Lieutenant Neil Templeton.

McCauley was a sort of "everyman" character who was viewed in the show as the most experienced and illustrious astronaut. As depicted in the scripts, the low-key but decisive McCauley was ubiquitous, assigned to every important space mission over at least a decade, including the earliest manned flights, the first flight to the moon, many additional moon landings and moon base construction missions, construction of a space station, and two flights to Mars (neither succeeded, and folklore has it that plans for a never-aired second season would have focused on further missions to Mars and beyond).

In many episodes, the astronauts were faced with accidents or technical problems that required innovation. The program was not idealistic; missions sometimes failed and astronauts sometimes died. For example, a scientist-astronaut stricken with a coronary thrombosis while exploring the moon was not expected to survive the G-forces of the return flight, so his comrades stowed the space-suited patient in a steel drum filled with water, to cushion him during launch. A "Space Race" episode involved spacecraft from the USA and USSR starting out almost simultaneously on the first Mars mission, with one of the craft aborting its effort to rescue the other craft and crew after it experienced problems.

The series included an episode whose plot essentially paralleled the ill-fated Apollo 13 mission's explosion in space more than a decade later, and another that was an uncanny foretelling of the accident that befell the real Gemini VIII mission in 1966.

Scripts often considered the human factor, and while action was the show's forte, humor and romance were part of the mix. Men Into Space predicted women astronauts and scientists, and married couples in space.

The series was advertised as being for its era an extremely accurate preview of manned spaceflight, based on scientific studies and buttressed by technical assistance from the USAF's ballistic missile and space medicine offices. The spacecraft designs, however, veered inconsistently between early 1950s Wernher Von Braun concepts, and later, totally scaled-down proposals.[clarification needed] Visual backdrops and conceptual designs of spacecraft, space stations and a moon base depended somewhat on contributions from notable astronautics artist Chesley Bonestell. The series also availed itself of extensive documentary footage of early missile launches. It evoked the earlier Disney space exploration documentaries, which in turn owed their look and feel to a widely read, early 1950s series on the subject in the old Collier's Weekly magazine, where Bonestell's art also held sway.

Men Into Space, later syndicated as Space Challenge, used for its plots many technical and human problems anticipated by engineers and planners. For example, the show depicted attempts to refuel spacecraft by tanker in orbit, construction of a space telescope, an experiment to dispose of high level atomic waste by launching it into the sun, the search for life-sustaining frozen water on the moon, exploration and destruction of an asteroid whose orbit threatened Earth, and exo-fossil evidence of extraterrestrial life.

Although the series was modestly budgeted, it was cleverly mounted with what, for its era, were good special effects helmed by Louis DeWitt. Even decades later, the series can still be appreciated for its attention to detail and accurate physics.

A narrator explained in nearly every episode why the astronauts needed magnetic boots to walk in or upon their free-falling spacecraft, how a jet thruster backpack could propel an astronaut through the vacuum of space, why a wrong angle of attack could doom a spacecraft upon atmosphericre-entry, and so forth. The spacecraft in the program were shown gliding to a powerless landing on a dry lake bed, just like the real Space Shuttle nearly 25 years later.

On the other hand, the show repeatedly depicted sound in the vacuum of space. Airlocks hummed, rockets roared, explosions boomed, and footsteps on the moon's surface could be heard.